The primary goal of the Transgenic/Embryonic Stem Cell Core Unit is to facilitate the application of murine transgenic technologies and embryo manipulation to the studies of as described in the various scientific projects in the program. This will entail the production of transgenic mice by standard techniques of DNA microinjection in one-cell embryos, and homologous recombination in embryonic stem (ES) cells combined with blastocyst-mediated transgenesis. Toward these ends, this core will also provide advice and expertise in the design, assembly and preparation of transgenes for microinjection and of DNA constructs to be used for homologous recombination. Assistance will also be provided in analysis of patterns of gene expression in the resulting genetically modified animals and/or ES cells. Additionally, this core will develop new methodologies and pursue their application within the individual projects in the program. This core developmental function will include in vitro differentiation of wild type and mutant ES cells, and analysis of chimeric animals resulting from ES cell injections into blastocysts.